84-1239-27　Ubiquitin Carboxyl-terminal Hydrolase Isozyme L1 (UCH-L1, UCHL1, Neuron Cytoplasmic Protein 9.5, PGP 9.5, PGP9.5, Ubiquitin Thioesterase L1) 100ul　031440

特徴

• Ubiquitin C-terminal hydrolase 1 (UCHL1) has several other names, such as ubiquitin carboxyl esterase L1, ubiquitin thiolesterase, neuron-specific protein PGP9.5 and Park5.
• It was originally identified as a major component of the neuronal cytoplasm from 2-dimensional gel analysis of brain tissues, and was given the name PGP9.5 (1).
• The protein is extremely abundant, and was estimated to be present at a concentration of 200-500 micrograms/g wet weight, representing a major protein component of neuronal cytoplasm (1).
• This has been claimed to represent 1-2% of total brain protein.
• It was later found that a ubiquitin C-terminal hydrolase enzyme activity was associated with the PGP9.5 protein, resulting in the renaming of PGP9.5 to ubiquitin C-terminal hydrolase 1.
• This is the first of a family of ubiquitin C-terminal hydrolases which have been characterized, and is expressed heavily in neurons in the brain.
• The ubiquitin C-terminal hydrolases cleave ubiquitin from other molecules.
• This activity is important to generate mono-ubiquitin from genes which encode polyubiquitin chains or ubiquitin fused to other proteins.
• The activity is also important to remove ubiquitin from partially degraded proteins, allowing the ubiquitin monomer to be recycled.
• Regulation of the ubiquitin pathway is very important and many disease states are associated with defects in this pathway.
• The covalent ubiquitin conjugates may then be degraded in the proteasome.
• Genetic knockout of UCHL1 in mice results in a motor neuron degeneration similar to the spontaneous gracile axonal dystrophy (gad) mutant mice (3).
• The gad mice have point mutations in the UCHL1 gene.
• Point mutations in the UCHL1 gene are associated with some forms of human Parkinson's disease (4).
• Recent studies suggest that UCHL1 also has a ubiqutinyl ligase activity, being able to couple ubiquitin monomers by linking the C-terminus of one with lysine 63 of the other (3).
• Since UCHL1 is heavily expressed in neurons, antibodies to UCHL1 can be used to identify neurons in histological sections and in tissue culture.
• The great abundance of this protein in neurons means that it is released from neurons in large amounts following injury or degeneration, so the detection of of UCHL1 in CSF and other bodily fluids can be used as a biomarker.
• UCHL1 was also discovered as a gene mutated in some rare famial forms of Parkinson's disease.
• Park5 was characterized as the gene causative of this form of Parkinson's and on analysis the Park5 gene proved to encode an I93M point mutations in the UCHL1 gene, which reduces the ubiquitin hydrolase activity.
• Interestingly a common allelic variant of UCHL1, the S18Y polymorphism is actually protective against Parkinson's disease.
• For a recent excellent review co-authored by the discoverer of UCHL1/Pgp9.5 (5).
• The HGNC name for this protein is UCHL1.
• Applications:Suitable for use in Immunofluorescence and Western Blot.
• A suitable control tissue is rat spinal cord or peripheral nerve homogenate.
• The UCHL1 protein runs at about 24kD on SDS-PAGE gels, and is a prominent component of brain, spinal cord and especially cortical extracts.
• Other applications not tested.
• Recommended Dilution:Immunofluorescence: 1:500Western Blot: 1:2000Optimal dilutions to be determined by the researcher.
• Storage and Stability:May be stored at 4°C for short-term only.
• Aliquot to avoid repeated freezing and thawing.
• Store at -20°C.
• Aliquots are stable for 12 months.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.